Tam et al. BMC Pediatrics 2014, 14:149 http://www.biomedcentral.com/1471-2431/14/149
RESEARCH ARTICLE
Open Access
Comparison of clinical and biochemical markers of dehydration with the clinical dehydration scale in children: a case comparison trial Ron K Tam1, Hubert Wong2, Amy Plint1, Nathalie Lepage3 and Guido Filler4*
Abstract Background: The clinical dehydration scale (CDS) is a quick, easy-to-use tool with 4 clinical items and a score of 1–8 that serves to classify dehydration in children with gastroenteritis as no, some or moderate/severe dehydration. Studies validating the CDS (Friedman JN) with a comparison group remain elusive. We hypothesized that the CDS correlates with a wide spectrum of established markers of dehydration, making it an appropriate and easy-to-use clinical tool. Methods: This study was designed as a prospective double-cohort trial in a single tertiary care center. Children with diarrhea and vomiting, who clinically required intravenous fluids for rehydration, were compared with minor trauma patients who required intravenous needling for conscious sedation. We compared the CDS with clinical and urinary markers (urinary electrolytes, proteins, ratios and fractional excretions) for dehydration in both groups using receiver operating characteristic (ROC) curves to determine the area under the curve (AUC). Results: We enrolled 73 children (male = 36) in the dehydration group and 143 (male = 105) in the comparison group. Median age was 32 months (range 3–214) in the dehydration and 96 months (range 2.6-214 months, p < 0.0001) in the trauma group. Median CDS was 3 (range 0–8) within the dehydration group and 0 in the comparison group (p < 0.0001). The following parameters were statistically significant (p < 0.05) between the comparison group and the dehydrated group: difference in heart rate, diastolic blood pressure, urine sodium/potassium ratio, urine sodium, fractional sodium excretion, serum bicarbonate, and creatinine measurements. The best markers for dehydration were urine Na and serum bicarbonate (ROC AUC = 0.798 and 0.821, respectively). CDS was most closely correlated with serum bicarbonate (Pearson r = −0.3696, p = 0.002). Conclusion: Although serum bicarbonate is not the gold standard for dehydration, this study provides further evidence for the usefulness of the CDS as a dehydration marker in children. Trial registration: Registered at ClinicalTrials.gov (NCT00462527) on April 18, 2007. Keywords: Gastroenteritis, Dehydration, Cystatin C, Microalbumin/creatinine ratio, Bicarbonate
Background Dehydration associated with gastroenteritis represents one of the leading causes of admission and morbidity in the pediatric emergency department (ED) [1]. It is also the most common cause of electrolyte abnormalities in children presenting at the ED [1,2]. In Canada, acute gastroenteritis accounts for 240,000 annual pediatric visits to the ED [3], while globally, diarrheal disease is * Correspondence: [email protected] 4 Department of Pediatrics, Western University, 800 Commissioners Road East, London, ON N6A 5W9, Canada Full list of author information is available at the end of the article
responsible for approximately 10% of deaths in children under 5 years of age [4]. Considering its extensive global impact, it is not surprising that there are several serious complications associated with severe dehydration including hypo-volemic shock, pre-renal acute kidney injury, and acute tubular necrosis. Clinicians must determine whether patients only need to be rehydrated or whether they face more substantial morbidity, which can be challenging. Consequently, there has been considerable interest in developing a simple, non-invasive tool for measuring the severity of dehydration in children. Although previous studies have attempted to validate markers of dehydration
© 2014 Tam et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Tam et al. BMC Pediatrics 2014, 14:149 http://www.biomedcentral.com/1471-2431/14/149
Page 2 of 9
by assessing the severity of dehydration using serial measurements of patient body weight [5,6], serial weights in sick and dehydrated children may be unreliable due to a number of factors that are not related to the severity of their illness. The clinical dehydration scale (CDS, Table 1) has been developed to meet this important objective [7,8]. The CDS combines scores of general appearance, eyes, mucous membranes, and tears. Use of the CDS has increased and it has been validated in 3 prospective studies, including one in the original ED [7], in a different Canadian pediatric ED [9], and in a multicenter trial at 3 Canadian EDs [10]. Following the development of the scale in 2004, Goldman et al., the originators of the scale, were first to attempt to validate the scale in a paper published in 2008 [7]. Their prospective observational study consisted of 205 children between 1 month and 5 years of age with suspected acute gastroenteritis. Since the original scale was developed using children 1–36 months of age, the aim of this study was to test this scale in a new cohort of children. Although the investigators found the dehydration categories of the scale to have a statistically significant correlation with length of stay (LOS) from time of arrival in triage and intravenous (i.v.) fluid rehydration, this study had numerous limitations: (i) it was only conducted in one center; (ii) it had a small number of children with moderate/severe dehydration; (iii) using LOS as an endpoint is questionable because LOS is multifactorial; (iv) staff may have changed their practices because of the study (Hawthorne effect), and, most importantly; (v) only a small number of the study population had blood tests performed, so the team could not validate their hypothesis that the dehydration categories positively correlated with abnormal serum pH values or bicarbonate levels (a primary outcome of the study). They indicated that future research is needed to provide information on this hypothesis. A second study attempting to validate the CDS in a different emergency department was published in June of 2010 [9]. With 150 patients from 1 month to 5 years of age diagnosed with gastroenteritis, enteritis, or gastritis, the primary outcome of this study was LOS after
being seen by the attending physician and the perceived need for IV fluid administration. Although serum bicarbonate and CO2 were measured, this was one of several secondary outcomes. Here, the correlation was statistically significant between the CDS and LOS from seeing the physician, perceived need for IV rehydration, and utilization of laboratory blood tests. Measured serum bicarbonate and CO2 were not found to significantly vary between the categories. Once again, this study had multiple limitations, the most important being that LOS is multifactorial, and although this was measured from the time the patient saw the physician, confounding factors may have still played a role. Last, Gravel et al. [10] performed a multicenter validation of the CDS, published a few months later in October 2010. 264 children between the ages of 1 month and 5 years were recruited at 3 Canadian centers, presenting for acute vomiting and/or diarrhea. The primary outcome of this study was percent dehydration (difference in weight), while secondary outcomes included proportion of blood test measurements, IV use, hospitalization, and inter-rater agreement. This study found a statistically significant correlation between the CDS and percent dehydration (by weight), number of blood test measurements, IV rehydration use, hospitalization, and abnormal plasma bicarbonate. This study was limited in that it did not exclusively include patients with a gastroenteritis diagnosis, though a subgroup analysis was performed producing similar results, and the primary outcome could not be measured in 45 (17%) of patients. Finally, the use of percent dehydration is limited by certain confounders. Although these studies have further validated this measure of dehydration, the primary outcome has differed in each study and all possess limitations (particularly LOS), none have employed the use of a comparison group (all 3 studies used a CDS score of 0 – “no dehydration” – for baseline measurements rather than a separate, non-dehydrated group), nor have they included a wide array of surrogate markers. The limitations of the preceding studies suggest the need for additional tests of validity for the CDS using other clinical markers.
Table 1 Clinical dehydration scale for children with acute gastroenteritis used for the study Characteristic
Score of 0
Score of 1
Score of 2
General appearance
Normal
Thirsty, restless, or lethargic, but irritable when touched
Drowsy, limp, cold, or sweaty; comatose or not
Eyes
Normal
Slightly sunken
Very sunken
Mucous membranes (tongue)
Moist
Sticky
Dry
Tears
Tears
Decreased tears
Absent tears
The CDS consists of four clinical characteristics (general appearance, eyes, mucous membranes, and tears), each of which are scored 0, 1, or 2 for a total score of 0 to 8, with 0 representing no dehydration; 1 to 4, some dehydration; and 5 to 8, moderate/severe dehydration. This score has been validated externally and is robust. We used exactly the same criteria as Benoit Bailey et al., Academic Emergency Medicine, 2010:17(6):583-88.
Tam et al. BMC Pediatrics 2014, 14:149 http://www.biomedcentral.com/1471-2431/14/149
We prospectively compared several established and novel markers of dehydration in two cohorts of children: a gastroenteritis group with dehydration and a comparison group without dehydration. Measuring the biomarkers in a comparison group provided baseline values and allowed us to validate the biomarkers in a healthy population prior to validating them in the dehydration cohort. The comparison group was comprised of patients with minor musculoskeletal injuries who were otherwise well and who required intravenous access for procedural treatment. We intended to validate the CDS by testing whether it correlates with certain factors, including bicarbonate, sodium, and others, and confirming its superiority to clinical impression.
Methods This study was designed as a case comparison trial and was registered at ClinicalTrials.gov (NCT00462527). It was conducted in a single center tertiary care pediatric emergency setting in Eastern Ontario. The study was supported through a grant to RT and GF from the Physicians’ Services Incorporated Foundation. Data used for this study was originally collected during a trial devised to examine the role of cystatin C as a biomarker of renal dysfunction in children with dehydration. Results were obtained from a secondary analysis of this data. Following approval by the Children’s Hospital of Eastern Ontario Research Ethics Board, written informed consent was obtained from patients (consenting minors) and caregivers. Patient enrollment took place between May 2007 and April 2008. All eligible pediatric patients (
RESEARCH ARTICLE
Open Access
Comparison of clinical and biochemical markers of dehydration with the clinical dehydration scale in children: a case comparison trial Ron K Tam1, Hubert Wong2, Amy Plint1, Nathalie Lepage3 and Guido Filler4*
Abstract Background: The clinical dehydration scale (CDS) is a quick, easy-to-use tool with 4 clinical items and a score of 1–8 that serves to classify dehydration in children with gastroenteritis as no, some or moderate/severe dehydration. Studies validating the CDS (Friedman JN) with a comparison group remain elusive. We hypothesized that the CDS correlates with a wide spectrum of established markers of dehydration, making it an appropriate and easy-to-use clinical tool. Methods: This study was designed as a prospective double-cohort trial in a single tertiary care center. Children with diarrhea and vomiting, who clinically required intravenous fluids for rehydration, were compared with minor trauma patients who required intravenous needling for conscious sedation. We compared the CDS with clinical and urinary markers (urinary electrolytes, proteins, ratios and fractional excretions) for dehydration in both groups using receiver operating characteristic (ROC) curves to determine the area under the curve (AUC). Results: We enrolled 73 children (male = 36) in the dehydration group and 143 (male = 105) in the comparison group. Median age was 32 months (range 3–214) in the dehydration and 96 months (range 2.6-214 months, p < 0.0001) in the trauma group. Median CDS was 3 (range 0–8) within the dehydration group and 0 in the comparison group (p < 0.0001). The following parameters were statistically significant (p < 0.05) between the comparison group and the dehydrated group: difference in heart rate, diastolic blood pressure, urine sodium/potassium ratio, urine sodium, fractional sodium excretion, serum bicarbonate, and creatinine measurements. The best markers for dehydration were urine Na and serum bicarbonate (ROC AUC = 0.798 and 0.821, respectively). CDS was most closely correlated with serum bicarbonate (Pearson r = −0.3696, p = 0.002). Conclusion: Although serum bicarbonate is not the gold standard for dehydration, this study provides further evidence for the usefulness of the CDS as a dehydration marker in children. Trial registration: Registered at ClinicalTrials.gov (NCT00462527) on April 18, 2007. Keywords: Gastroenteritis, Dehydration, Cystatin C, Microalbumin/creatinine ratio, Bicarbonate
Background Dehydration associated with gastroenteritis represents one of the leading causes of admission and morbidity in the pediatric emergency department (ED) [1]. It is also the most common cause of electrolyte abnormalities in children presenting at the ED [1,2]. In Canada, acute gastroenteritis accounts for 240,000 annual pediatric visits to the ED [3], while globally, diarrheal disease is * Correspondence: [email protected] 4 Department of Pediatrics, Western University, 800 Commissioners Road East, London, ON N6A 5W9, Canada Full list of author information is available at the end of the article
responsible for approximately 10% of deaths in children under 5 years of age [4]. Considering its extensive global impact, it is not surprising that there are several serious complications associated with severe dehydration including hypo-volemic shock, pre-renal acute kidney injury, and acute tubular necrosis. Clinicians must determine whether patients only need to be rehydrated or whether they face more substantial morbidity, which can be challenging. Consequently, there has been considerable interest in developing a simple, non-invasive tool for measuring the severity of dehydration in children. Although previous studies have attempted to validate markers of dehydration
© 2014 Tam et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Tam et al. BMC Pediatrics 2014, 14:149 http://www.biomedcentral.com/1471-2431/14/149
Page 2 of 9
by assessing the severity of dehydration using serial measurements of patient body weight [5,6], serial weights in sick and dehydrated children may be unreliable due to a number of factors that are not related to the severity of their illness. The clinical dehydration scale (CDS, Table 1) has been developed to meet this important objective [7,8]. The CDS combines scores of general appearance, eyes, mucous membranes, and tears. Use of the CDS has increased and it has been validated in 3 prospective studies, including one in the original ED [7], in a different Canadian pediatric ED [9], and in a multicenter trial at 3 Canadian EDs [10]. Following the development of the scale in 2004, Goldman et al., the originators of the scale, were first to attempt to validate the scale in a paper published in 2008 [7]. Their prospective observational study consisted of 205 children between 1 month and 5 years of age with suspected acute gastroenteritis. Since the original scale was developed using children 1–36 months of age, the aim of this study was to test this scale in a new cohort of children. Although the investigators found the dehydration categories of the scale to have a statistically significant correlation with length of stay (LOS) from time of arrival in triage and intravenous (i.v.) fluid rehydration, this study had numerous limitations: (i) it was only conducted in one center; (ii) it had a small number of children with moderate/severe dehydration; (iii) using LOS as an endpoint is questionable because LOS is multifactorial; (iv) staff may have changed their practices because of the study (Hawthorne effect), and, most importantly; (v) only a small number of the study population had blood tests performed, so the team could not validate their hypothesis that the dehydration categories positively correlated with abnormal serum pH values or bicarbonate levels (a primary outcome of the study). They indicated that future research is needed to provide information on this hypothesis. A second study attempting to validate the CDS in a different emergency department was published in June of 2010 [9]. With 150 patients from 1 month to 5 years of age diagnosed with gastroenteritis, enteritis, or gastritis, the primary outcome of this study was LOS after
being seen by the attending physician and the perceived need for IV fluid administration. Although serum bicarbonate and CO2 were measured, this was one of several secondary outcomes. Here, the correlation was statistically significant between the CDS and LOS from seeing the physician, perceived need for IV rehydration, and utilization of laboratory blood tests. Measured serum bicarbonate and CO2 were not found to significantly vary between the categories. Once again, this study had multiple limitations, the most important being that LOS is multifactorial, and although this was measured from the time the patient saw the physician, confounding factors may have still played a role. Last, Gravel et al. [10] performed a multicenter validation of the CDS, published a few months later in October 2010. 264 children between the ages of 1 month and 5 years were recruited at 3 Canadian centers, presenting for acute vomiting and/or diarrhea. The primary outcome of this study was percent dehydration (difference in weight), while secondary outcomes included proportion of blood test measurements, IV use, hospitalization, and inter-rater agreement. This study found a statistically significant correlation between the CDS and percent dehydration (by weight), number of blood test measurements, IV rehydration use, hospitalization, and abnormal plasma bicarbonate. This study was limited in that it did not exclusively include patients with a gastroenteritis diagnosis, though a subgroup analysis was performed producing similar results, and the primary outcome could not be measured in 45 (17%) of patients. Finally, the use of percent dehydration is limited by certain confounders. Although these studies have further validated this measure of dehydration, the primary outcome has differed in each study and all possess limitations (particularly LOS), none have employed the use of a comparison group (all 3 studies used a CDS score of 0 – “no dehydration” – for baseline measurements rather than a separate, non-dehydrated group), nor have they included a wide array of surrogate markers. The limitations of the preceding studies suggest the need for additional tests of validity for the CDS using other clinical markers.
Table 1 Clinical dehydration scale for children with acute gastroenteritis used for the study Characteristic
Score of 0
Score of 1
Score of 2
General appearance
Normal
Thirsty, restless, or lethargic, but irritable when touched
Drowsy, limp, cold, or sweaty; comatose or not
Eyes
Normal
Slightly sunken
Very sunken
Mucous membranes (tongue)
Moist
Sticky
Dry
Tears
Tears
Decreased tears
Absent tears
The CDS consists of four clinical characteristics (general appearance, eyes, mucous membranes, and tears), each of which are scored 0, 1, or 2 for a total score of 0 to 8, with 0 representing no dehydration; 1 to 4, some dehydration; and 5 to 8, moderate/severe dehydration. This score has been validated externally and is robust. We used exactly the same criteria as Benoit Bailey et al., Academic Emergency Medicine, 2010:17(6):583-88.
Tam et al. BMC Pediatrics 2014, 14:149 http://www.biomedcentral.com/1471-2431/14/149
We prospectively compared several established and novel markers of dehydration in two cohorts of children: a gastroenteritis group with dehydration and a comparison group without dehydration. Measuring the biomarkers in a comparison group provided baseline values and allowed us to validate the biomarkers in a healthy population prior to validating them in the dehydration cohort. The comparison group was comprised of patients with minor musculoskeletal injuries who were otherwise well and who required intravenous access for procedural treatment. We intended to validate the CDS by testing whether it correlates with certain factors, including bicarbonate, sodium, and others, and confirming its superiority to clinical impression.
Methods This study was designed as a case comparison trial and was registered at ClinicalTrials.gov (NCT00462527). It was conducted in a single center tertiary care pediatric emergency setting in Eastern Ontario. The study was supported through a grant to RT and GF from the Physicians’ Services Incorporated Foundation. Data used for this study was originally collected during a trial devised to examine the role of cystatin C as a biomarker of renal dysfunction in children with dehydration. Results were obtained from a secondary analysis of this data. Following approval by the Children’s Hospital of Eastern Ontario Research Ethics Board, written informed consent was obtained from patients (consenting minors) and caregivers. Patient enrollment took place between May 2007 and April 2008. All eligible pediatric patients (
